Immunostaining for p16/Ki-67 (CINtec® Plus, Roche Ventana, Mannheim, Germany) is valuable for the triage of borderline and low-grade cytological abnormalities as well as of HPV-high-risk (HR) -positive, cytologically negative or HPV-HR-negative, cytologically positive cases. We analyzed the correlation between the p16/Ki-67 status of patients before biopsy/therapy with histologically confirmed CIN 2 and 3 and invasive cervical carcinoma.
All cases of a German routine lab in which histology had been performed in 2012 and in 2013 and which had a test of HPV-HR (cobas®, Roche Diagnostics, Mannheim, Germany) and p16/Ki-67, both carried out maximally six months earlier, are reported. Histology followed colposcopically directed biopsy, conization or hysterectomy. p16/ Ki-67 tests were made out of cervical smears taken in liquid based cytology medium (PreservCyt®, Hologic, Wiesbaden, Germany) according to the manufactures instructions.
In 2012, in 674 of 1167 CIN 2+ cases (57.8%) and in 2013, in 578 of 1004 CIN 2+ cases (57.6%) a p16/Ki-67 result was available. For both years together in CIN 2 270 (94.73%), in CIN 3 939 (99.8%) and in cervical cancer 26 (100%) cases were p16/Ki-67 positive. In all histologically confirmed CIN 2+ cases we found 11 HPV-HR-negative CIN 2 (2.57%), 23 HPV-HR-negative CIN 3 (1.85%) and 5 HPV-HR-negative (10.5%) invasive cervical cancer cases. In 27 from 39 (69%) HPV-HR-negative cases a p16/Ki-67 cotest was available. 7 of 8 CIN 2 (87.5%), 17 of 18 CIN 3 (95%) and 1 of 1 (100%) cervical cancer HPV-HR-negative cases were p16/Ki-67 positive.
The large majority of histologically confirmed CIN 2 and 3 and cervical cancers were positive for the biomarker p16/Ki-67 when tested in cervical smears < 6 months before biopsy/therapy. In 25 from 27 (93%) HPV-negative cases with p16/Ki-67 cotesting the p16/Ki-76 test was positive. 965 from 967 (99.8%) of all histologically confirmed CIN 3+ lesions tested with p16/Ki67 were positive